COCO, also known as DAND5, Dante, and CKTSF1B3, is a member of the DAN Domain family of BMP antagonists that includes DAN (DAND1), Gremlin/Drm (DAND2), PRDC (Protein Related to Dan and Cerberus; DAND3), and Cerberus (DAND4). DAN family members contain a cysteine-knot domain that is homologous to that found in other TGF-beta superfamily ligands (1-3). BMPs play important roles in tissue morphogenesis and development processes (4-6). The human COCO cDNA encodes a 189 amino acid (aa) precursor with a 22 aa signal sequence (2, 7). COCO has eight Cys residues in the cysteine-knot which places it in the CAN subfamily of BMP antagonists along with the other DAN family proteins (1). Human COCO shares 60% and 24% aa sequence identity with mouse and Xenopus COCO, respectively. It shares 17%, 20%, 25%, and 22% aa sequence identity with human DAN, Gremlin, PRDC, and Cerberus, respectively. In Xenopus embryonal development, COCO is expressed by pluripotent ectodermal cells. Expression is abruptly downregulated prior to gastrulation, and the loss of ectodermal cell pluripotency is coincident with COCO downregulation (7). COCO binds and inhibits Xnr1, BMP-4, Activin, and Wnt-8 (7). In mouse, COCO expression is elevated on the right side of Henson’s node at the early somite stage, in contrast to the left side expression of Nodal (8). COCO may cooperate with Nodal in gastrulation and embryonic left-right axis formation (5, 8).